GnRH Agonist Administration Research Articles

Gonadotropin-releasing hormone agonists for ovarian protection during cancer chemotherapy: systematic review and meta-analysis.

To evaluate the effectiveness of gonadotropin-releasing hormone agonist (GnRHa) administration before and/or during cancer chemotherapy for the protection of ovarian reserve in premenopausal women without prior diagnosis of infertility. This was a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing administration of GnRHa before and/or during chemotherapy vs chemotherapy alone. Eligible participants were premenopausal women at any stage of cancer, without previous diagnosis of infertility. An electronic database search in MEDLINE, CENTRAL, LILACS and ClinicalTrials.gov was performed. After selecting eligible studies, the relative risk (RR) was assessed for primary ovarian insufficiency (POI)/amenorrhea and for spontaneous pregnancy after completion of treatment. Thirteen RCTs comparing concurrent use of GnRHa and chemotherapy (609 participants) with chemotherapy alone (599 participants) were eligible for meta-analysis. All trials were open-label and patients had been treated for breast cancer (n = 1099) or lymphoma (n = 109). GnRHa had a significant benefit on the risk of POI/amenorrhea (RR, 0.60; 95% CI, 0.45-0.79), which persisted in subgroup analysis for breast cancer (RR, 0.57; 95% CI, 0.43-0.77) but not for lymphoma patients (RR, 0.70; 95% CI, 0.20-2.47). The rate of spontaneous pregnancy after completion of treatment was higher in women receiving GnRHa plus chemotherapy compared with those receiving chemotherapy alone (RR, 1.43; 95% CI, 1.01-2.02). Overall, the quality of evidence was low due to the unclear risk of bias, short follow-up and lack of objective assessment of ovarian function and reserve. Evidence, albeit of low quality, supports the use of GnRHa before and/or during chemotherapy to reduce the risk of POI and increase the probability of spontaneous pregnancy in the short term. Further high quality RCTs with more accurate assessment of ovarian reserve are needed to support definitive recommendations for clinical practice. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Low-dose hCG as trigger day and 35 hr later have different ovarian hyperstimulation syndrome occurrence in females undergoing In vitro fertilization: An RCT

Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication, which can cause high morbidity and mortality. Use of gonadotropin releasing hormone (GnRH) agonist instead of human chorionic gonadotropin (hCG) in GnRH antagonist cycles causes luteinizing hormone surge by GnRH stimulation which reduces the risk of OHSS by reducing the total amount of gonadotropin; however, there is no possibility of transferring fresh embryos. The current study aimed to evaluate the effect of hCG along with GnRH agonist administration in the occurrence of OHSS and pregnancy rate in females undergoing in vitro fertilization. The current randomized clinical trial was conducted on 80 cases in 2 groups. Gonal-F was used to stimulate the oocyte from the second day of menstruation. When follicle size was 12-14 mm, GnRH antagonist was added to the protocol till the detection of more than two follicles greater than 18 mm. Then, GnRH agonist was added to the protocol as a trigger. In group A, 35 hr after the administration of GnRH agonist, the low-dose human hCG, 1500 IU, was used. In group B, low-dose hCG, 1500 IU, was used at the same time by GnRH agonist administration. The rate of pregnancy, OHSS, and its severity were compared between 2 groups within 2 wk. There was no significant difference regarding chemical and clinical pregnancies between the 2 groups. Severe OHSS was significantly higher in group B (p= 0.03). Administration of hCG 35 hr after GnRH agonist administration results in lower rate of severe OHSS.

Postlaparoscopic GnRHagonist Therapy does not Improve Spontaneous Conception Rates of Women with Endometriosis

Objective: To investigate the reproductive benefits of combining laparoscopic surgery with GnRH-agonist hormonal therapy in treating women with endometriosis.
 Methods: This is a non-randomized prospective analytic study of patients with endometriosis conducted in a private hospital in Bandung during the period of January 2014 to December 2015, whom were later followed up after 12-24 months for assessment of post-surgical reproductive performance. A total of 121 patients were enrolled, 60 of which received post-surgical GnRH-agonist hormonal therapy.
 Results: We discovered that 56 women (46.3%) eventually achieved spontaneous conception after surgery but upon further analysis, it was discovered that GnRH-agonist played no significantly meaningful role in improving the spontaneous pregnancy rates of these patients (OR 1.539; 95% CI 0.750-3.159; p-value 0.239). Furthermore, even though there was a wide range as to when they achieved conception, those untreated with hormonal therapy tended to conceive far more quickly than those who were (5.91 ± 6.28; 8.56 ± 4.24; p-value: 0.011).
 Conclusion: Post-laparoscopic GnRH-agonist administration to women with endometriosis does not significantly improve their chances of spontaneous conception. In fact, such administration seems to delay it.
 [Indones J Obstet Gynecol 2017; 5-2: 87-93]
 Keywords: endometriosis, GnRH-agonist, laparoscopy

Perspectives on the co-treatment with GnRHa in female patients undergoing hematopoietic stem cell transplantation.

Outcomes after hematopoietic stem cell transplantation (HSCT) for patients with both malignant and nonmalignant diseases have improved significantly in recent years. However, the endocrine system is highly susceptible to damage by the high-dose chemotherapy and/or irradiation used in the conditioning regimen before HSCT. Ovarian failure and subsequent infertility are frequent complications that long-term HSCT survivors and their partners face with a negative impact on their QoL. Several meta-analyses of randomized clinical trials showed that gonadotropin-releasing hormone agonist (GnRHa) administration in advance of starting standard chemotherapy decreases the risk of gonadal dysfunction and infertility in cancer patients, but GnRHa use for ovarian protection in HSCT patients is not fully determined. In this review, we are discussing the potential preservation of ovarian function and fertility in pubertal girls/premenopausal women who undergo HSCT using GnRHa in parallel with conditioning chemotherapy, focusing on the current data available and making some special remarks regarding the use of GnRHa.

Does GnRH Agonist Triggering Control Painful Symptom Scores During Assisted Reproductive Technology? A Retrospective Study.

The aim of this study was to assess the progression of pain symptoms during assisted reproductive technology (ART) cycles following administration of GnRH agonist (GnRHa) versus human chorionic gonadotrophin (hCG) triggering. Observational cohort study. A tertiary care university hospital in France. Patients who underwent ART programs. Between January 01, 2014, and June 31, 2014, 122 cycles were allocated to 2 groups: GnRHa triggering with a scheduled differed embryo transfer (n = 57) or hCG triggering with a fresh embryo transfer (n = 70). Pelvic pain scores were evaluated using a visual analog scale (VAS) with regard to dysmenorrhea, dyspareunia, noncyclic pelvic pain, gastrointestinal, and lower urinary tract pain. The total VAS score was defined as the sum of the scores for the various symptoms. Evaluations were carried out twice: during the synchronization treatment prior to ovarian stimulation and during a final evaluation 3 weeks postretrieval. The data were processed using univariate and multivariate logistic regression models. Trends for total VAS change (ie, final VAS score - synchronization VAS score). For both groups, pain increased during the ART procedure. Trends for the total VAS change revealed that the increase in pain was significantly less in the "GnRHa triggering" group compared to the "hCG triggering" group (3.77 ± 7.73 and 6.50 ± 6.57, P < .05, respectively). Multivariate logistic regression indicated that GnRHa triggering was associated with less of an increase in pain compared to hCG triggering (odds ratio = 0.31, 95% confidence interval 0.13-0.71, P < .05). Compared to hCG, GnRHa triggering limits pain symptom progression in the period immediately after ART.

Final follicular maturation by administration of GnRH agonist plus HCG versus HCG in normal responders in ART cycles: An RCT

Gonadotropin-releasing hormone agonists (GnRH-a) was increasingly used for triggering oocyte maturationfor the prevention of ovarian hyperstimulation syndrome. Studies suggest that GnRH-a might be used as a better trigger agent since it causes both Luteinizing hormone and follicle stimulating hormone release from a physiologic natural cycle. The aim of this study was to evaluate the effect of dual-triggering in assisted reproductive technology outcomes. 192 normal responder women aged ≤42 years and 18< Body Mass Index <30 kg/m2 enrolled in this single-blind randomized controlled trial. All participants received antagonist protocol. For final triggering, women randomly were divided into two groups. Group, I was triggered by 6500 IU human chorionic gonadotropin (hCG) alone, and group II by 6500 IU hCG plus 0.2 mg of triptorelin. The implantation, chemical, clinical and ongoing pregnancy, and abortion rates were measured. The mean of retrieved oocytes and obtained embryos were statistically higher in the dual-trigger group (group I), but the implantation and pregnancy rates were similar in two groups. The results of our study did not confirm the favorable effect of dual-triggered oocyte maturation with a GnRH-a and a standard dosage of hCG as an effective strategy to optimize pregnancy outcome for normal responders in GnRH-antagonist cycles. We think that this new concept requires more studies before becoming a universal controlled ovarian hyperstimulation protocol in in vitro fertilization practice.

Impact of Mid-Luteal Phase GnRH Agonist Administration on Reproductive Outcomes in GnRH Agonist-Triggered Cycles: A Randomized Controlled Trial.

To explore whether the addition of a mid-luteal bolus of GnRH agonist (GnRHa) improves the implantation rate (IR) in in vitro fertilization (IVF) cycles. A randomized controlled trial. Private IVF center. 328 IVF/intracytoplasmic sperm injection patients were triggered with GnRHa and received 1,500 IU HCG on the day of oocyte pick-up (OPU) in addition to a standard luteal phase support (LPS). In addition, the study group received a bolus of GnRHa 6 days after OPU, whereas the control group did not. Implantation rate. Ongoing pregnancy (OP) and live birth (LB) rates. Although serum concentrations of FSH, LH, E2, and P on day OPU + 7 were significantly higher in the study group compared to the control group, the IR was not statistically different between the treatment group (27%) and the control group (23%) [odds ratio (OR) 1.2 (95% CI 0.9-1.7), P < 0.27]. Similarly, the OP rate was 37% in the treatment group and 31% in the control group [OR 1.3 (95% CI 0.8-2.0), P < 0.23]. The LB rate was 36% in the treatment group and 31% in the control group [OR: 1.3 (95% CI 0.8-2.0), P < 0.27]. Although a trend toward a higher IR and pregnancy rate was observed in the treatment group, this difference was not statistically significant. However, the absolute risk difference of 5% found for LB is clinically relevant, warranting further investigation. 02053779.

GnRH agonist administration prior to embryo transfer in freeze-all cycles of patients with endometriosis or aberrant endometrial integrin expression

Prolonged gonadotrophin-releasing hormone agonist (GnRHa) administration before IVF with fresh embryo transfer to patients with endometriosis or aberrant endometrial integrin expression (-integrin) improves outcomes but may suppress ovarian response and prevents elective cryopreservation of all embryos. This retrospective cohort pilot study evaluates freeze-all cycles with subsequent prolonged GnRHa before embryo transfer in these populations. Patients from 2010 to 2015 who met inclusion criteria and received a long-acting GnRHa every 28 days twice before FET were evaluated. A subset underwent comprehensive chromosomal screening (CCS) after trophectoderm biopsy. Three groups were identified: Group 1: + CCS, +endometriosis (20 patients, 20 transfers); Group 2: +CCS, −integrin (12 patients, 13 transfers); Group 3: no CCS, +endometriosis or −integrin (10 patients, 12 transfers); Group 4: all transfers after CCS for descriptive comparison only (n = 2809). Baseline characteristics were similar among Groups 1–3 except that the mean surgery to oocyte aspiration interval was longer for Group 1 than Group 3. Implantation and ongoing pregnancy rates were statistically similar among the three groups and compared favourably to Group 4. A non-significant trend towards improved outcomes was noted in Group 1. Prolonged GnRHa after freeze-all in these patients avoids excessive ovarian suppression and results in excellent outcomes.

Impact of blood hypercoagulability on in vitro fertilization outcomes: a prospective longitudinal observational study

BackgroundBlood coagulation plays a crucial role in the blastocyst implantation process and its alteration may be related to in vitro fertilization (IVF) failure. We conducted a prospective observational longitudinal study in women eligible for IVF to explore the association between alterations of coagulation with the IVF outcome and to identify the biomarkers of hypercoagulability which are related with this outcome.MethodsThirty-eight women eligible for IVF (IVF-group) and 30 healthy, age-matched women (control group) were included. In the IVF-group, blood was collected at baseline, 5–8 days after administration of gonadotropin-releasing hormone agonist (GnRH), before and two weeks after administration of human follicular stimulating hormone (FSH). Pregnancy was monitored by measurement of βHCG performed 15 days after embryo transfer. Thrombin generation (TG), minimal tissue factor-triggered whole blood thromboelastometry (ROTEM®), procoagulant phospholipid clotting time (Procoag-PPL®), thrombomodulin (TMa), tissue factor activity (TFa), factor VIII (FVIII), factor von Willebrand (FvW), D-Dimers and fibrinogen were assessed at each time point.ResultsPositive IVF occurred in 15 women (40%). At baseline, the IVF-group showed significantly increased TG, TFa and TMa and significantly shorter Procoag-PPL versus the control group. After initiation of hormone treatment TG was significantly higher in the IVF-positive as compared to the IVF-negative group. At all studied points, the Procoag-PPL was significantly shorter and the levels of TFa were significantly higher in the IVF-negative group compared to the IVF-positive one. The D-Dimers were higher in the IVF negative as compared to IVF positive group. Multivariate analysis retained the Procoag-PPL and TG as predictors for the IVF outcome.ConclusionsDiagnosis of women with hypercoagulability and their stratification to risk of IVF failure using a model based on the Procoag-PPL and TG is a feasible strategy for the optimization of IVF efficiency that needs to be validated in prospective trials.

Efficacy of single-dose gonadotropin-releasing hormone agonist administration prior to magnetic resonance-guided focused ultrasound surgery for symptomatic uterine fibroids.

To investigate the effects of a single-dose GnRHa on the thermal ablation of MRgFUS in women with symptomatic fibroids. In this pilot study, a single-dose GnRHa was administered in 17 patients with a total of 20 fibroids. Volume and scaled signal intensity (SSI) as an objective marker of fluid contents were prospectively followed up with serial MR scans. The control group of 17 patients with 19 fibroids were retrospectively enrolled and compared with GnRHa group in terms of non-perfused volume (NPV) and thermal dosimetry to assess the efficiency of thermal ablation. About 29days after GnRHa administration, SSI and volume of fibroids were reduced by 55.1 and 10.6%, respectively (p<0.05) but no adverse events were reported. NPV per unit energy (0.046cm3/J±0.026 vs. 0.031cm3/J±0.018, p=0.041) was larger and SSI (8.4±8.0 vs. 13.9±12.0, p=0.053) was lower in GnRHa group. Linear regression analysis showed that these two parameters were in a reverse correlation (p=0.011). GnRHa is supposed to reduce the fluid contents of fibroids including blood vessels and enhance the tissue responsiveness to thermal energy. A single dose prior to MRgFUS has the potential to improve treatment efficiency, while avoiding the side effects of multiple doses of GnRHa.

P258 - Benefit of Gonadotropin-releasing Hormone (GnRH) agonist administration with Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2-Negative subtype for young breast cancer patients

P258 - Benefit of Gonadotropin-releasing Hormone (GnRH) agonist administration with Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2-Negative subtype for young breast cancer patients

The effect of estradiol on granulosa cell responses to FSH in women with polycystic ovary syndrome

BackgroundThe influence of estradiol (E2) on granulosa cell (GC) function has not been tested clinically in women with polycystic ovary syndrome (PCOS). The objective of this study is to determine if E2 influences GC responses to FSH in women with PCOS.MethodsThis is a two phase, single cohort study conducted over a 2-year period at a single academic center. Nine women with PCOS according to NIH criteria. In Phase 1, FSH stimulation of GC responses as measured by E2 and Inhibin B (Inh B) were assessed before and at 5 and 6 weeks after GnRH agonist administration. In Phase 2, the same protocol was employed with the addition of an aromatase inhibitor (letrozole, LET) administered daily beginning at week 4 for 2 weeks.ResultsIn Phase 1, recovery of FSH, E2 and Inh B from ovarian suppression occurred at 5 and 6 weeks after GnRH agonist injection and preceded resumption of LH and androgen secretion. In Phase 2, hormone recovery after GnRH agonist was characterized by elevated FSH and suppressed E2 levels whereas recovery of LH and androgen levels were unchanged. In Phase 1, FSH stimulated E2 and Inh B responses were unaltered during recovery from ovarian suppression. In Phase 2, E2 and Inh B fold changes after FSH were significantly reduced at weeks 5 (p < 0.04) and 6 (p < 0.01), respectively.ConclusionIn anovulatory women with PCOS, chronic, unopposed E2 secretion may contribute, at least in part, to enhanced ovarian responsiveness to FSH.Trial registrationNCT02389088

Administration of gonadotropin-releasing hormone agonist on Day 5 increases luteal blood flow and improves pregnancy prediction accuracy on Day 14 in recipient Holstein cows.

This study assessed the effects of gonadotropin-releasing hormone (GnRH) treatment on Day 5 (Day 0 = estrus) on luteal blood flow and accuracy of pregnancy prediction in recipient cows. On Day 5, 120 lactating Holstein cows were randomly assigned to a control group (n = 63) or GnRH group treated with 100 μg of GnRH agonist (n = 57). On Days 3, 5, 7, and 14, each cow underwent ultrasound examination to measure the blood flow area (BFA) and time-averaged maximum velocity (TAMV) at the spiral arteries at the base of the corpus luteum using color Doppler ultrasonography. Cows with a corpus luteum diameter ≥ 20 mm (n = 120) received embryo transfers on Day 7. The BFA values in the GnRH group were significantly higher than those in the control group on Days 7 and 14. TAMV did not differ between these groups. According to receiver operating characteristic analyses to predict pregnancy, a BFA cutoff of 0.52 cm2 yielded the highest sensitivity (83.3%) and specificity (90.5%) on Day 7, and BFA and TAMV values of 0.94 cm2 and 44.93 cm/s, respectively, yielded the highest sensitivity (97.1%) and specificity (100%) on Day 14 in the GnRH group. The areas under the curve for the paired BFA and TAMV in the GnRH group were 0.058 higher than those in the control group (0.996 and 0.938, respectively; P < 0.05). In conclusion, GnRH treatment on Day 5 increased the luteal BFA in recipient cows on Days 7 and 14, and improved the accuracy of pregnancy prediction on Day 14.

Recurrence factors and reproductive outcomes of laparoscopic myomectomy and minilaparotomic myomectomy for uterine leiomyomas.

ObjectiveThe aim of this study was to determine recurrence factors and reproductive outcomes of laparoscopic myomectomy (LM) and minilaparotomic myomectomy (MM) for treating uterine leiomyomas.MethodsBetween 2007 and 2013, 160 patients underwent myomectomy, including 122 who underwent LM and 38 who underwent MM. Patients were followed up for recurrence based on pelvic ultrasound exams. Only patients who were followed up for a minimum of two years were selected for this retrospective study. Pregnancy rate, delivery, and delivery methods were compared between the two groups to evaluate reproductive outcomes. Furthermore, mean age, body mass index, preoperative administration of gonadotropin-releasing hormone agonist (GnRHa), and characteristics of leiomyomas were investigated to determine recurrence factors.ResultsThe mean body mass index in the MM group was significantly (P=0.048) higher than that in the LM group. The number and the largest diameter of removed leiomyoma were also significantly higher in the MM group (both P=0.001). Logistic regression after adjusting significantly different characteristics showed that the LM group had shorter (P=0.020) postoperative hospitalization days compared to the MM group. Other outcome variables including recurrence rate were not significantly different between the two groups. Reproductive outcomes such as pregnancy rate, delivery, and delivery methods were not significantly different between the two groups. Preoperative GnRHa therapy was the only significant (P=0.039) recurrence factor after myomectomy.ConclusionThis study showed that LM and MM had similar recurrence rates and reproductive outcomes. The only recurrence factor of significance was preoperative administration of GnRHa.

The Effect of Luteal-Phase Support with Triptrolin Administration on Implantation and Clinical Pregnancy Rate in Assisted Reproductive Technology

Background: Luteal phase support with GnRH agonist administration has been shown to be effective in improving the outcome of assisted reproductive technology. The goal of this study was to evaluate the effect of single dose Triptrolin (a GnRH agonist) on the probability of the clinical pregnancy rate following embryo transfer (ET) in assisted reproductive techniques (ART). Methods: In this double blinded randomized clinical trial, 340 infertile women who were candidates for intra-cytoplasmic sperm injection (ICSI) were randomly assigned to receive GnRH agonist (Triptrolin) in the luteal phase or placebo. In the intervention group, 0.1 mg Triptrolin was injected subcutaneously, while the control group received normal saline. The clinical pregnancy and implantation rate were compared between the two groups using chi-2 and t-test. P-values less than 0.05 were considered significant. The registration number of this clinical trial is IRCT 2014030916912N1. Results: Administration of 0.1 mg Triptrolin on day 6 after oocyte pick up showed no superiority over placebo in implantation (16.9% - 14%, P = 0.40) and clinical pregnancy rates (32% - 29%, P = 0.66), but the rate of clinical pregnancy was higher in women who were below 27 years of age and those with PCO. Conclusion: Administration of Triptrolin was not superior to placebo for luteal phase support.

A reduction in long-term spatial memory persists after discontinuation of peripubertal GnRH agonist treatment in sheep

Chronic gonadotropin-releasing hormone agonist (GnRHa) administration is used where suppression of hypothalamic-pituitary-gonadal axis activity is beneficial, such as steroid-dependent cancers, early onset gender dysphoria, central precocious puberty and as a reversible contraceptive in veterinary medicine. GnRH receptors, however, are expressed outside the reproductive axis, e.g. brain areas such as the hippocampus which is crucial for learning and memory processes. Previous work, using an ovine model, has demonstrated that long-term spatial memory is reduced in adult rams (45 weeks of age), following peripubertal blockade of GnRH signaling (GnRHa: goserelin acetate), and this was independent of the associated loss of gonadal steroid signaling. The current study investigated whether this effect is reversed after discontinuation of GnRHa-treatment. The results demonstrate that peripubertal GnRHa-treatment suppressed reproductive function in rams, which was restored after cessation of GnRHa-treatment at 44 weeks of age, as indicated by similar testes size (relative to body weight) in both GnRHa-Recovery and Control rams at 81 weeks of age. Rams in which GnRHa-treatment was discontinued (GnRHa-Recovery) had comparable spatial maze traverse times to Controls, during spatial orientation and learning assessments at 85 and 99 weeks of age. Former GnRHa-treatment altered how quickly the rams progressed beyond a specific point in the spatial maze at 83 and 99 weeks of age, and the direction of this effect depended on gonadal steroid exposure, i.e. GnRHa-Recovery rams progressed quicker during breeding season and slower during non-breeding season, compared to Controls. The long-term spatial memory performance of GnRHa-Recovery rams remained reduced (P<0.05, 1.5-fold slower) after discontinuation of GnRHa, compared to Controls. This result suggests that the time at which puberty normally occurs may represent a critical period of hippocampal plasticity. Perturbing normal hippocampal formation in this peripubertal period may also have long lasting effects on other brain areas and aspects of cognitive function.

Effect of luteal-phase gonadotropin-releasing hormone agonist administration on pregnancy outcome in IVF/ICSI cycles: a systematic review and Meta-analysis

Objective: To evaluate the potential efficacy and safety of gonadotropin-releasing hormone agonist(GnRH-a) administration in the luteal-phase on in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles in assisted reproductive technology (ART). Methods: The relevant papers published before November 2015 were electronically searched in PubMed, EMBASE, Cochrane Library, WHO ICTRP, ClinicalTrials.gov, CNKI, CBM and WanFang database to collect randomized controlled trial (RCT) involving GnRH-a administration in the luteal-phase on IVF/ICSI cycles in ART. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality according to the Cochrane Handbook. Then, Meta-analysis was performed using Stata 13.0. Results: A total of 3 406 patients, 3 280 IVF/ICSI cycles from 11 RCT were subjected to Meta-analysis. All cycles presented statistically significantly higher rates of live birth/ongoing pregnancy (RR=1.29, 95%CI: 1.11-1.51), clinical pregnancy (RR=1.24, 95%CI:1.08-1.43) and multiple pregnancy (RR=1.95, 95%CI:1.21-3.14) in patients who received luteal-phase GnRH-a administration compared with those who did not. Conclusions: These findings demonstrate that the luteal-phase GnRH-a administration could increase birth/ongoing pregnancy rate, clinical pregnancy rate and multiple pregnancy rate in all cycles, so it may be an ideal choice for luteal phase support in patients undergoing IVF/ICSI therapy.

Factors associated with ovarian function recovery after chemotherapy for breast cancer: a systematic review and meta-analysis.

Which factors related to patient, treatment or disease are associated with ovarian function recovery after chemotherapy in premenopausal women with breast cancer? Younger age and GnRH agonist (GnRHa) administration during chemotherapy were significantly associated with menses recovery, but this recovery was less likely in patients exposed to taxanes. To date, published meta-analyses have only assessed GnRHa administration as a possible factor for ovarian function recovery, and their results were conflicting. Current guidelines present distinct recommendations regarding the use of GnRHa for fertility preservation (FP) in women with breast cancer. A systematic review and meta-analysis of published studies in the English, Portuguese, French or Spanish languages (1990-2015), ongoing trials or completed trials (1990-2015) and conference proceedings (2000-2015) were performed. We searched the MEDLINE, Embase, LILACS, Scielo, Toxline and DART databases, online trial registries and conference proceedings. Studies were eligible if they included premenopausal women with early breast cancer treated with chemotherapy, reported ovarian function recovery data and identified factor(s) associated with recovery. Two authors independently screened the studies, extracted data and assessed the risk of bias. An odds ratio (OR) was estimated from the number of recovery events. A meta-analysis was conducted using a random-effects model. Fifteen articles were included. Five different factors were analysed: younger age and baseline levels of anti-Müllerian hormone (patient-related factors), co-administration of GnRHa, addition of taxanes to anthracycline-based chemotherapy and addition of endocrine therapy to chemotherapy (treatment-related factors). Menses recovery was the most used marker. Younger age (≤40 years) and exposure to GnRHa were positively associated with menses recovery (OR 6.07 and 2.03, respectively) but exposure to taxanes adversely affected recovery (OR 0.49). Significant heterogeneity among studies was found. A general limitation of the included studies is the use of menses as the main recovery marker. Regarding GnRHa, the substantial heterogeneity and conflicting results limit the interpretation of our results. Studies that use additional markers and have a longer follow-up are needed. The decision for using chemotherapy regimens with taxanes must take into account their potential adverse effects on female fertility. Considering the conflicting results regarding GnRHa agonist use, other fertility preservation strategies should also be considered. No external funding was received. There are no conflicts of interest to declare. This review was registered at PROSPERO (CRD42015013494).

Breast Cancer - Specifics of Gynecological Care and Counseling

This paper summarizes current knowledge about clinically important aspects of gynecological care in female breast cancer patients. Despite the overall positive acceptance of oral contraceptives and hormone replacement drugs, hormone therapy may raise fears of developing breast cancer. Specifics of gynecological care of fertile patients are discussed as these patients face ovarian failure when undergoing oncological treatment of breast cancer. Tamoxifen is used in adjuvant therapy of breast cancer, in metastatic breast cancer or as prophylaxis of breast cancer in high-risk patients. We aim to study the influence of hormonal treatment on breast cancer development in women with and without congenital predisposition. The main risk factors for developing breast cancer are family history, increased density of breast tissue, atypical hyperplasia of the breast and previous radiotherapy to the chest area. All these factors increase the relative risk of cancer more than four times. Contraceptives and hormone replacement therapy show generally less than two-fold or no increase at all (RR 0.96-1.6). We concentrate with safety of hormonal therapy in breast cancer patients after they finish breast cancer treatment in pre- and postmenopausal period. We discuss fertility-sparing methods for preservation of ovarian function due to oncological treatment. Those methods are cryopreservation of embryos, oocytes in metaphase II and ovarian tissue. Simultaneous administration of GnRH agonists may protect ovarian function before gonadotoxic chemotherapy. We describe in detail the effects of tamoxifen on gynecological organs in both pre- and postmenopausal women in relation to the potential risk of developing secondary malignancy. In premenopausal women, tamoxifen has no increased risk of cancer of the uterine body. In postmenopausal patients, the risk after five years of tamoxifen is increased 2-3 times. Transvaginal sonography is not the screening tool for detection of the pathology in the uterine cavity during tamoxifen therapy, and so we only recommend looking for symptoms. Hysteroscopy is the golden standard for the examination of the uterine cavity in symptomatic postmenopausal patients using tamoxifen. This paper summarizes the current knowledge in areas where oncological and gynecological cares for breast cancer patients mingle. It should lead to greater understanding and deepening cooperation between clinical oncologists and oncogynecologists for the benefit of our patients.Key words: adjuvant hormonal therapy - fertility preservation - GnRH analogs - contraceptives - endometrial hyperplasia - hormone replacement therapy - breast neoplasm - tamoxifenThis work was supported by the Czech Ministry of Health - RVO (FNBr, 65269705).The authors declare they have no potential confl icts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 6. 6. 2016Accepted: 22. 7. 2016.

GnRh Agonist Treatment Improves Implantation and Pregnancy Rates of Frozen-Thawed Embryos Transfer.

To study the effect of GnRh agonist administration prior to estrogen-progesterone preparation of the endometrium on the implantation rate in frozen-thawed embryo transfer (FET) cycles in infertile patients treated with IVF/ICSI. Prospective controlled study. Private center in Alexandria, Egypt. Patients undergoing frozen-thawed embryo transfer FET. Patients were divided into two groups, A and B. Group A patients consisted of 110 patients (110 cycles) who received daily subcutaneous injections of 0.1mg of the GnRh agonist triptorelin starting from the mid-luteal phase of the cycle preceding the actual FET cycle. The dose was reduced to 0.05mg from the second day of the cycle when daily oral estradiol valerate 6mg was also started. Daily vaginal supplementation of micronized progesterone 400mg b.d. was started after 12days when the GnRh agonist was also stopped. Frozen-thawed embryos were transferred on day+1 of their chronological age and when the endometrium reached 12mm in thickness. Group B consisted of 100 patients (100 cycles) who started daily estradiol valerate 6mg administration from the second day of the FET cycle and followed the same regimen but without prior treatment with triptorelin. Implantation and pregnancy rates were compared among the two groups. There was a significant increase in implantation rate in the GnRh agonist group (group A) compared to the estrogen and progesterone only group (group B) (44.1 vs. 21.1%; P=0.002*). The pregnancy rate was also significantly higher in group A compared to group B (65.5 vs. 42%, P=0.013*). GnRh agonist administration during endometrial preparation for FET increases the implantation and pregnancy rates.